Optical sensors can be used for monitoring oxygenation of blood or tissue. Optical sensor signals tend to be sensitive to motion because movement of the sensor alters the optical pathway of the sensor through a volume of tissue adjacent to the sensor. Measurements using optical sensors are particularly susceptible to motion artifact when the adjacent tissue is not a uniform, homogeneous tissue. Motion sensitivity of optical sensors makes monitoring of tissue oxygenation in a patient challenging, particularly in an ambulatory patient. However, tissue oxygenation monitoring can provide valuable data for use in diagnosing a patient condition and managing a therapy. A need remains for medical devices including optical sensors and associated methods for reliably monitoring tissue oxygenation in the presence of motion or other noise sources.